The principal aims of this research proposal are to determine whether follicle-stimulating hormone (FSH) secretion in cycling female rats is altered during the aging process and if so, why is it altered. Initial experiments are designed to characterize the pre-ovulatory (proestrous) and secondary (estrous) increases in circulating FSH levels during the 4-day estrous cycle in young (3 and 6 mos.) and middle-aged (9, 12 and 15 mos.) rats. If age-related alterations in FSH levels are observed, additional experiments will be conducted to determine the possible causes of altered FSH secretion. These studies will include: 1) measuring inhibin-like activity in ovarian venous plasma from young and middle-aged rats at various times on proestrus and estrus; 2) evaluating the responsiveness of the hypothalamo-pituitary unit to an inhibin-containing preparation (porcine follicular fluid) during the transition to aging; 3) testing the ovarian responsiveness to FSH in vitro with respect to inhibin production, and 4) evaluating the augmentative effects of steroids and the suppressive effects of non-steroidal substances on in vitro pituitary FSH secretion during the aging process. Since FSH has an important role in establishing a cohort of follicles for ovulation in subsequent cycles, it is anticipated that the results of these studies will provide valuable information concerning the possible etiology of reproductive aging. Future experiments may then be proposed which attempt to delay reproductive senescence by preventing age-related changes in FSH secretion. Moreover, since an alteration in FSH secretion is one of the first hormonal changes occurring at the onset of the human menopause, the proposed experiments and their results will be extremely relevant to the clinical practitioner's understanding of the events leading to the age-related decline in fertility. Finally, it is hoped that the data obtained from such studies may aid the gynecologist in devising a treatment which would effectively regulate the erractic nature of menstrual cycles normally observed during the menopausal transition.